Preparation of substituted-2,3-dicarboxypyridinium nitrates

ABSTRACT

There are provided crystalline substituted-2,3-dicarboxypyridinium nitrate salts, the preparation thereof and the use thereof in the isolation and purification of important substituted pyridinedicarboxylic acid herbicide intermediates.

This is a divisional of co-pending application, Ser. No. 07/967,349,filed on Oct. 28, 1992 now U.S. Pat. No. 5,284,955.

BACKGROUND OF THE INVENTION

Substituted 2,3-pyridinedicarboxylic acids are important intermediatesin the manufacture of highly effective 2-(2-imidazolin-2-yl)nicotinateherbicides. Among the methods to prepare substituted2,3-pyridinedicarboxylic acids is the nitric acid oxidation of theappropriately substituted quinoline precursor. However, certainsubstituted pyridinedicarboxylic acids are difficult to isolate from thespent nitric acid solution. Such compounds do not readily precipitatefrom the product solution.

The compound, 2,3-dicarboxypyridinium nitrate is described by P. Sutterand C. Weis in the Journal of Heterocyclic Chemistry, 23 p. 29-32(1986), however no substituted 2,3-dicarboxypyridinium nitrates arefound therein.

Therefore, it is an object of this invention to provide crystallinesubstituted 2,3-dicarboxypyridinium nitrate compounds which are usefulin the isolation and purification of important 2,3-pyridinedicarboxylicacid herbicide intermediates. It is another object of this invention toprovide a means for producing the desired substitutedpyridinedicarboxylic acid herbicide intermediates in improved yield andpurity.

It is a feature of this invention that the desired dicarboxylic acidproduct may be obtained without necessitating a quenching step, therebyallowing the spent nitric acid to be recycled and eliminating the costlyand potentially hazardous presence of solvent wastes.

SUMMARY OF THE INVENTION

The present invention provides a substituted 2,3-dicarboxypyridiniumnitrate compound of formula I ##STR1## wherein Y and Z are eachindependently hydrogen, C₁ -C₆ alkyl optionally substituted with one ormore

C₁ -C₄ alkoxy, halogen or sulfonyl groups, nitro, formyl, C₁ -C₄alkylcarbonyl, C₁ -C₄ alkylsulfonyl or phenyl optionally substitutedwith

C₁ -C₄ alkyl, C₁ -C₄ alkylsulfonyl, halogen, or haloalkyl groups

with the proviso that one of Y or Z must be other than hydrogen,

or when taken together Y and Z may form a ring wherein YZ is representedby the structure ##STR2##

L, M, q and R are each independently hydrogen,

C₁ -C₄ alkyl, C₁ -C₄ alkoxy, C₁ -C₄ alkylsulfonyl.sub., C₁ -C₄haloalkyl, nitro, phenyl optionally substituted with one C₁ -C₄ alkyl orhalogen group or phenoxy optionally substituted with one halogen, C₁ -C₄alkyl, nitro or CF₃ group with the proviso that only one of L, M, Q or Rmay represent a substituent other than hydrogen, halogen, C₁ -C₄ alkylor C₁ -C₄ alkoxy.

The invention further provides a method for the preparation of a formulaI pyridinium nitrate compound which comprises reacting a substitutedquinoline compound of formula II ##STR3## wherein Y and Z are asdescribed for formula I above and R₁, R₂, R₃ and R₄ are eachindependently hydrogen, (II) hydroxy, nitro, amino, SO₃ H or SO₃ Cl withthe proviso that one of R₁, R₂, R₃ or R₄ is other than hydrogen; withnitric acid optionally in the presence of a catalytic amount ofManganese and a nitroaromatic solvent, at an elevated temperature toform a reaction mixture and concentrating the reaction mixture to givethe crystalline formula I compound.

The formula I dicarboxypyridinium nitrate is readily converted to thecorresponding pyridinedicarboxylic acid upon treatment with a solvent orsolvent mixture. The thus-obtained, high purity pyridinedicarboxylicacid is an important intermediate in the production of2-(2-imidazolin-2-yl)nicotinate herbicidal agents. Descriptions of thesehighly effective herbicidal agents and the use of substituted2,3-pyridinedicarboxylic acid in their preparation can be found in U.S.Pat. No. 4,798,619 among others.

A method to prepare substituted 2,3-pyridinedicarboxylic acid via thenitric acid oxidation of the appropriate quinoline precursor in thepresence of a Manganese catalyst is described in co-pending patentapplication Ser. No. 07/967,350, filed Oct. 28, 1992 and incorporatedherein by reference thereto.

DETAILED DESCRIPTION OF THE INVENTION

The Skraup reaction is a well-known and convenient source of the formulaII substituted quinoline starting material used in the manufacture ofsubstituted 2,3-pyridinedicarboxylic acid herbicide intermediates. TheSkraup reaction is carried out in an aqueous acidic solution.Advantageously, it has now been found that crude Skraup reactionmixtures, without undue and tedious isolation procedures, may be used asa source of starting material in the nitric acid oxidation of formula IIquinoline compounds to produce high purity substituted2,3-pyridinedicarboxylic acid products. Surprisingly, it has been foundthat concentration of the spent nitric acid solution in the presence ofa nitroaromatic solvent such as nitrobenzene or nitroxylenes yields acrystalline nitrate salt of formula I in high yield. The formula Idicarboxypyridinium nitrate is easily converted to the desired2,3-pyridinedicarboxylic acid upon treatment with a second solvent orsolvent mixture. The desired oxidation product is thus obtained withoutthe need to quench the reaction solution and thereby allowing for therecyclization of the spent nitric acid. The procedure is illustrated inFlow Diagram I. ##STR4## The formula I dicarboxypyridinium nitratecompounds of the invention allow the isolation and purification ofimportant herbicide intermediate compounds. Many of the desired2,3-pyridinedicarboxylic acid compounds are difficult to isolate fromthe spent nitric acid solution resulting from the oxidation procedure.Even after quenching the nitric acid with reagents such as formic acidor isopropanol and/or adjusting the pH of the reaction mixture, certainsubstituted pyridinedicarboxylic acids (e.g. 5-ethylpyridinedicarboxylic acid) do not readily precipitate from solution.High concentration of the quenched nitric acid product solution resultsin exotherms, product decomposition, NO_(x) gas emission and potentiallyexplosive mixtures. Surprisingly, the substituted pyridinedicarboxylicacid compound crystallizes from solution as the pure nitric acidaddition salt in high yield when the spent nitric acid oxidationreaction solution is concentrated in the presence of a nitroaromaticsolvent such as nitrobenzene or nitroxylenes such as 3-nitro-o-xylene.Therefore, the presence of costly and potentially hazardous solventwastes are eliminated.

In actual practice, a formula II quinoline compound, either isolated orpresent as a crude reaction product solution, optionally in the presenceof a solvent, is added to a mixture of 70% nitric acid and a catalyticamount of Manganese at a temperature range of about 50°-150° C. to forma reaction mixture, the reaction mixture is heated at 50°-150° C. untilthe oxidation is complete. The unquenched reaction mixture is treateddirectly with a nitroaromatic solvent such as nitrobenzene,3-nitro-o-xylene and the like and concentrated in vacuo to give theformula I dicarboxypyridinium nitrate compound as a crystallineprecipitate. The pyridinium nitrate precipitate is isolated byfiltration and converted to the corresponding free2,3-pyridinedicarboxylic acid by treatment with a second solvent orsolvent system.

Suitable solvents for the conversion of the formula Idicarboxypyridinium nitrate to the corresponding2,3-pyridinedicarboxylic acid are ketones such as methyl isobutylketone, acetone and the like, mixtures of a ketone and a halogenatedhydrocarbon such as methylene chloride, chloroform, ethylene dichlorideand the like and water and mixtures of water and a co-solvent such as aketone or halogenated hydrocarbon. Treatment of the formula I pyridiniumnitrate compound of the invention with a suitable solvent or solventmixture yields the desired substituted 2,3-pyridinedicarboxylic acid ingood yield and high purity.

The invention herein described is further illustrated by the followingExamples and is not to be deemed limited thereby except as defined inthe claims. Unless otherwise, noted all parts are parts by weight. Theterm HPLC designates high performance liquid chromatography.

EXAMPLE 1

Preparation of 2,3-dicarboxy-5-ethylpyridinium nitrate ##STR5## Amixture of 70% nitric acid (480 g, 5.33 mole) and manganese dioxide (0.1g, 1.75 mmole) is heated to 95° C., treated with a solution of3-ethyl-8hydroxyquinoline (51.5 g, 67.5% pure, 0.20 mole) in 100 gnitrobenzene over a 2 hour period, held at 90°-100° C. for 10 hours,cooled to room temperature, treated with an additional 200 g ofnitrobenzene, concentrated in vacuo to a total weight of about 240 g andfiltered. The filter cake is washed with nitrobenzene and methylenechloride and dried in vacuo to give the title product as a white solid,49.2 g (95.3% yield), mp 109°-111° C. The product is used as is inExample 2.

EXAMPLE 2

Preparation of 5-ethyl-2,3-pyridinedicarboxylic acid ##STR6## Thenitrate salt obtained in Example 1 is dispersed in a mixture of 100 mLof methylene chloride and 100 mL of methyl isobutyl ketone, heated atreflux temperature for 1 hour, cooled to room temperature and filtered.The filter cake is washed with a 1:1 mixture of methylenechloride:methyl isobutyl ketone and dried in vacuo to give5-ethyl-2,3-pyridinedicarboxylic acid, 34.6 g, (89% isolated yield from3-ethyl-8-hydroxyquinoline), 94.5% pure by HPLC.

EXAMPLE 3

Preparation of substituted 2,3-dicarboxypyridinium nitrate

Using essentially the same procedure described in Example 1 andemploying the appropropriate substituted quinoline precursor, thefollowing dicarboxypyridinium nitrate compounds are obtained:

    ______________________________________                                         ##STR7##                                                                     Y                Z     mp °C.                                          ______________________________________                                        CH.sub.3         H     167-168                                                H                H     155-158                                                CH.sub.2 OCH.sub.3                                                                             H     92-94                                                  ______________________________________                                    

EXAMPLE 4

Preparation of 5-ethyl-2,3-pyridinedicarboxylic acid in high purity fromcrude 3-ethyl-8-hydroquinoline starting material via the isolation of2,3-dicarboxy-5-ethylpyridinium nitrate ##STR8## A mixture of 70% nitricacid and a catalytic amount of maganaese dioxide is treated with asolution of crude (67.5% pure) 3-ethyl-8-hydroxyquinoline (EHQ) innitrobenzene (NBz) or 3-nitro-9-xylene (3-NOX) at 95° C., heated at90°-100° C. until oxidation is complete, cooled to room temperature,concentrated in vacuo in the presence of the nitroaromatic solvent andfiltered to give 2,3-dicarboxy-5-ethylpyridinium nitrate. Thethus-isolated nitrate salt is dispersed in a 1:1 mixture of methylenechloride (CH₂ C₁₂) and methyl isobutyl ketone (MIBK) or acetone and CH₂C₁₂ and filtered to give the desired 5-ethyl-2,3-pyridinedicarboxylicacid in high purity.

Varying the above reaction parameters and the solvent systems used toliberate the free pyridinedicarboxylic acid compound from the isolateddicarboxypyridinium nitrate, the following results are obtained andshown in Table I.

                  TABLE I                                                         ______________________________________                                        Preparation of 5-Ethyl-2,3-pyridinedicarboxylic Acid                                   HNO.sub.3                                                            Molar Ratio                                                                            Oxid'n   Nitrate Salt % Yield %                                      HNO.sub.3 :EHQ                                                                         Solvent  Dispersant   from EHQ                                                                              Purity                                 ______________________________________                                        16       3-NOX    3-NOX/HCOOH  83.3    78.1                                   16       3-NOX    3-NOX/HCOOH  84.2    78.2                                   16       NBz      MIBK         74.9    98.0                                   16       3-NOX    MIBK         75.7    93.5                                   16       NBz      MIBK/HCOOH   73.0    96.3                                   16       3-NOX    MIBK/HCOOH   78.5    94.4                                   16       3-NOX     MIBK/HCOOH* 83.8    95.4                                   16       3-NOX    MIBK/CH.sub.2 Cl.sub.2                                                                     86.2    91.9                                   16       3-NOX    MIBK/CH.sub.2 Cl.sub.2                                                                     90.5    91.4                                   16       3-NOX    MIBK/CH.sub.2 Cl.sub.2                                                                     80.4    93.1                                   18       3-NOX    MIBK/CH.sub.2 Cl.sub.2                                                                     80.6    90.9                                   18       NBz      MIBK/CH.sub.2 Cl.sub.2                                                                     83.8    94.5                                    18**    NBz      MIBK/CH.sub.2 Cl.sub.2                                                                     55.4    91.2                                   16       3-NOX    Acetone      72.1    97.7                                   16       3-NOX    Acetone/CH.sub.2 Cl.sub.2                                                                  67.8    96.5                                   18       3-NOX    Acetone/CH.sub.2 Cl.sub.2                                                                  64.4    97.3                                   ______________________________________                                         *Water extraction                                                             **Starting material was not isolated from Skraup reaction mixture        

I claim:
 1. A method for the preparation of a compound of formula I##STR9## wherein Y and Z are each independently hydrogen, C₁ -C₆ alkyloptionally substired with one or moreC₁ -C₄ alkoxy, halogen or sulfonylgroups, nitro, C₁ -C₄ alkylcarbonyl, C₁ -C₄ alkylsulfonyl or phenyloptionally substituted with C₁ -C₄ alkyl, C₁ -C₄ alkylsulfonyl, halogen,or haloalkyl groups with the proviso that one of Y or Z must be otherthan hydrogen, or when taken together Y and Z may form a ring wherein YZis represented by the structure ##STR10## L, M, Q and R are eachindependently hydrogen, C₁ -C₄ alkyl, C₁ -C₄ alkoxy, C₁ -C₄alkylsulfonyl, C₁ -C₄ haloalkyl, nitro, phenyl optionally substitutedwith one C₁ -C₄ alkyl or halogen group or phenoxy optionally substitutedwith one halogen, C₁ -C₄ alkyl, nitro or CF₃ group with the proviso thatonly one of L, M, Q or R may represent a substituent other thanhydrogen,halogen, C₁ -C₄ alkyl or C₁ -C₄ alkoxy which comprises reactinga compound of formula II ##STR11## wherein Y and Z are described forformula I above and R₁, R₂, R₃ and R₄ are each independently hydrogen,hydroxy, nitro, amino, SO₃ H or S03C1 with the proviso that at least oneof R₁, R₂, R₃ and R₄ is other than hydrogen; with nitric acid optionallyin the presence of a catalytic amount of Manganese at an elevatedtemperature to form a reaction mixture and concentrating the reactionmixture in the presence of a nitroaromatic solvent to give thecrystalline formula I compound.
 2. The method according to claim 1wherein the Manganese is present as KMnO₄ or MnO₂.
 3. The methodaccording to claim 1 wherein the nitroaromatic solvent is nitrobenzene.4. The method according to claim 1 wherein the nitroaromatic solvent is3-nitro-o-xylene.
 5. The method according to claim 1 wherein theelevated temperature is about 50°-150° C.
 6. The method according toclaim 1 for the preparation of the compound of formula I wherein Y is C₁-C₆ alkyl or hydrogen and Z is hydrogen.
 7. The method according toclaim 1 for the preparation of the compound of formula I wherein Y ismethoxymethyl or halomethyl and Z is hydrogen.
 8. The method accordingto claim 1 wherein the nitroaromatic solvent is part of the reactionmixture.